Dengue viruses (DENV), members of the genus Flavivirus, are the most common cause of mosquito-borne viral diseases in tropical and subtropical regions around the world. Approximately 50 to 100 million people per year are infected with DENV. DENV infections may be asymptomatic, but most often manifest as dengue fever (DF), a self-limited disease. Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are more severe, life-threatening manifestations of dengue infection. DENV imposes one of the largest social and economic burdens of any mosquito-borne viral pathogen. There is no specific treatment for infection, and control of dengue virus by vaccination has proved elusive. The pathogenesis of DHF/DSS is not completely understood. There are four serotypes of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4). Infection with one serotype confers lifelong homotypic immunity, but only short term (approximately three to six months) cross protection against heterotypic serotypes.
The risk of severe disease is greatest during secondary, heterotypic infections in subjects with more than one circulating serotype. There is evidence that prior infection with one type can produce an antibody response that can intensify, or enhance, the course of disease during a subsequent infection with a different serotype. The possibility that vaccine components could elicit enhancing antibody responses, as opposed to protective responses, has been a major concern in designing and testing vaccines to protect against dengue infections. There is thus a need for a vaccine that may be effective against different serotypes and which does not enhance the course of the DENV infection.